Chimeric antigen receptor (car)-t cell expressing cxcl12 receptor

Abstract

This invention provides, as a therapeutic method for eradication of neoplastic diseases of the blood with poor diagnosis, a cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane, and an agent and a pharmaceutical composition having anti-tumor activity, which comprises such cell.

1 . A cell co-expressing a chimeric antigen receptor (CAR) protein and a CXCL12 receptor protein on the cell membrane. 
     
     
         2 . The cell according to  claim 1 , wherein the CXCL12 receptor is CXCR4. 
     
     
         3 . The cell according to  claim 1 , wherein the chimeric antigen receptor (CAR) protein targets a cell surface antigen selected from among CD25 (IL-2 receptor alpha chain), CD19, and CD7. 
     
     
         4 . The cell according to any  claim 1 , which is a T cell. 
     
     
         5 . An agent exhibiting anti-tumor activity, which comprises the cell according to  claim 1 . 
     
     
         6 . The agent according to  claim 5 , which is used in combination with a further anti-tumor agent and/or anti-tumor therapy. 
     
     
         7 . A pharmaceutical composition comprising the agent according to  claim 5  and a pharmaceutically acceptable carrier. 
     
     
         8 . The agent according to  claim 5 , for the treatment and/or the prevention of relapse of a neoplastic disease selected from the group consisting of acute myeloid leukemia (AML), adult T cell leukemia, B-cell acute lymphatic leukemia (B-ALL), T-cell acute lymphatic leukemia (T-ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CIVIL), Hodgkin's lymphoma, and non-Hodgkin's lymphoma. 
     
     
         9 . A method for preparing the cell according to  claim 1 , which comprises introducing a first polynucleotide encoding a chimeric antigen receptor (CAR) protein and a second polynucleotide encoding a CXCL12 receptor protein into a cell. 
     
     
         10 . The method according to  claim 9 , wherein the chimeric antigen receptor (CAR) protein targets a cell surface antigen selected from among CD25 (IL-2 receptor alpha chain), CD19, and CD7. 
     
     
         11 . The method according to  claim 9 , wherein the first polynucleotide and the second polynucleotide are introduced into a cell by the same vector or separate vectors. 
     
     
         12 . A method for the treatment and/or the prevention of relapse of a neoplastic disease in a subject, which comprises a step of administering a cell co-expressing a chimeric antigen receptor (CAR) protein targeting CD25 (IL-2 receptor alpha chain) and a CXCL12 receptor protein on the cell membrane to the subject. 
     
     
         13 . The method according to  claim 12 , wherein the chimeric antigen receptor (CAR) protein targets a cell surface antigen selected from among CD25 (IL-2 receptor alpha chain), CD19, and CD7. 
     
     
         14 . The method according to  claim 12 , wherein the neoplastic disease is selected from the group consisting of acute myeloid leukemia (AML), adult T cell leukemia, B-cell acute lymphatic leukemia (B-ALL), T-cell acute lymphatic leukemia (T-ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CIVIL), Hodgkin's lymphoma, and non-Hodgkin's lymphoma. 
     
     
         15 . The method according to  claim 12 , wherein the cell is administered once to a subject. 
     
     
         16 . The method according to  claim 12 , wherein the cell is administered in the range of 10 4  to 10 9  cells per kg body weight of the subject. 
     
     
         17 . The method according to  claim 12 , which further comprises a step of measuring the expression level of a target cell surface antigen in a tumor cell of the subject before the step of administering the cell. 
     
     
         18 . The method according to  claim 12 , which further comprises a step of evaluating therapeutic effects after the step of administering the cell. 
     
     
         19 . The method according to  claim 18 , wherein the therapeutic effect is evaluated based on one or more indices selected from (i) decrease in tumor cells in the blood, (ii) decrease in tumor cells in the bone marrow, (iii) decrease in tumor cells in the spleen, and (iv) suppression of tumor cell infiltration into the liver, in the subject. 
     
     
         20 .- 23 . (canceled) 
     
     
         24 . The pharmaceutical composition according to  claim 7 , for the treatment and/or the prevention of relapse of a neoplastic disease selected from the group consisting of acute myeloid leukemia (AML), adult T cell leukemia, B-cell acute lymphatic leukemia (B-ALL), T-cell acute lymphatic leukemia (T-ALL), mixed phenotype acute leukemia (MPAL), chronic myeloid leukemia (CML), Hodgkin's lymphoma, and non-Hodgkin's lymphoma.